Peripheral T-lymphocytes express WNT7A and its restoration in leukemia-derived lymphoblasts inhibits cell proliferation

<p>Abstract</p> <p>Background</p> <p>WNT7a, a member of the Wnt ligand family implicated in several developmental processes, has also been reported to be dysregulated in some types of tumors; however, its function and implication in oncogenesis is poorly understood. Moreover, the expression of this gene and the role that it plays in the biology of blood cells remains unclear. In addition to determining the expression of the <it>WNT7A </it>gene in blood cells, in leukemia-derived cell lines, and in samples of patients with leukemia, the aim of this study was to seek the effect of this gene in proliferation.</p> <p>Methods</p> <p>We analyzed peripheral blood mononuclear cells, sorted CD3 and CD19 cells, four leukemia-derived cell lines, and blood samples from 14 patients with Acute lymphoblastic leukemia (ALL), and 19 clinically healthy subjects. Reverse transcription followed by quantitative Real-time Polymerase chain reaction (qRT-PCR) analysis were performed to determine relative <it>WNT7A </it>expression. Restoration of WNT7a was done employing a lentiviral system and by using a recombinant human protein. Cell proliferation was measured by addition of WST-1 to cell cultures.</p> <p>Results</p> <p>WNT7a is mainly produced by CD3 T-lymphocytes, its expression decreases upon activation, and it is severely reduced in leukemia-derived cell lines, as well as in the blood samples of patients with ALL when compared with healthy controls (<it>p </it>≤0.001). By restoring <it>WNT7A </it>expression in leukemia-derived cells, we were able to demonstrate that WNT7a inhibits cell growth. A similar effect was observed when a recombinant human WNT7a protein was used. Interestingly, restoration of <it>WNT7A </it>expression in Jurkat cells did not activate the canonical Wnt/β-catenin pathway.</p> <p>Conclusions</p> <p>To our knowledge, this is the first report evidencing quantitatively decreased <it>WNT7A </it>levels in leukemia-derived cells and that <it>WNT7A </it>restoration in T-lymphocytes inhibits cell proliferation. In addition, our results also support the possible function of <it>WNT7A </it>as a tumor suppressor gene as well as a therapeutic tool.</p

Discrete-time non-linear state observer based on a super twisting-like algorithm

The properties of robustness and finite-time convergence provided by sliding mode (SM) theory have motivated several researches to deal with the problems of control and state estimation. In the SM theory, the super-twisting algorithm (STA), a second-order SM scheme, has demonstrated remarkable characteristics when it is implemented as a controller, observer or robust signal differentiator although the presence of noise and parametric uncertainties. However, the design of this algorithm was originally developed for continuous-time systems. The growth of microcomputers technology has attracted the attention of researchers inside the SM discrete-time domain. Recently, discretisations schemes for the STA were studied using majorant curves. In this study, the stability analysis in terms of Lyapunov theory is proposed to study a discrete-time super twisting-like algorithm (DSTA) for non-linear discrete-time systems. The objective is to preserve the STA characteristics of robustness in a quasi-sliding mode regime that was proved in terms of practical Lyapunov stability. An adequate combination of gains obtained by the same Lyapunov analysis forces the convergence for the DSTA. The problem of state estimation is also analysed for second-order mechanical systems of n degrees of freedom. Simulation results regarding the design of a second-order observer using the DSTA for a simple pendulum and a biped model of seven degrees of freedom are presented

Simultaneous state and parameter estimation method for a conventional ozonation system

This article presents a simultaneous state (via a nonlinear form of Luenberger observer) and parameter (using a proportional–integral least mean square form) estimator design method for a conventional ozonation system. The suggested state observer assumes that the only available output signal is the concentration of the ozone gas at the output of the reactor. The estimation of the reaction rate constants of ozonation in the presence of contaminants uses the suggested proportional–integral estimation method. The convergence proof of the developed state-parameter identification method was confirmed using a Lyapunov based stability analysis. This analysis characterizes the quality of estimation considering the presence of modeled uncertainties and external perturbations. The implementation of the super-twisting algorithm as a robust and exact differentiator allowed to perform the estimation of the reaction rate constants of the ozonation, the temporal evolution of the dissolved ozone and the evolution of contaminants concentrations. The simultaneous state and parameter estimator design method was implemented in real-time using phenol as a model contaminant. The numerically simulated and real-time implementations showed that the method provides accurate estimates of the contaminant concentration and the reaction rate coefficient in all the evaluated cases

Identification and control of class of non-linear systems with non-symmetric deadzone using recurrent neural networks

In this study, a neuro-controller with adaptive deadzone compensation for a class of unknown SISO non-linear systems in a Brunovsky form with uncertain deadzone input is presented. Based on a proper smooth parameterisation of the deadzone, the unknown dynamics is identified by using a continuous time recurrent neural network whose weights are adjusted on-line by stable differential learning laws. On the basis of this neural model so obtained, a feedback linearisation controller is developed in order to follow a bounded reference trajectory specified. By means of Lyapunov analysis, the boundedness of all the closed-loop signals as well as the weights and deadzone parameter estimations is rigorously proven. Besides, the exponential convergence of the actual tracking error to a bounded zone is guaranteed. The effectiveness of this scheme is illustrated by a numerical simulation. � The Institution of Engineering and Technology 2014

Enhanced hydrogen production by a sequential dark and photo fermentation process : effects of initial feedstock composition, dilution and microbial population

Two-stage process of dark fermentation (DF) and photo fermentation (PF), using fruit and vegetable waste (FVW) and cheese whey powder (CWP), was used as an approach to enhance the hydrogen (H-2) production. FVW and CWP at C/N ratios of 34, 39, 60, 71 and 82 were tested as substrates for DF. Dilution (1:2, 1:5, 1:10) of the DF effluents was used as a coupling strategy. DF effluents with low-butyrate and high lactate concentrations were obtained as a function of an increased C/N ratio, which results in high H-2 production during the PF. Maximum overall H-2 yields of 793.7 and 695.4 mLH(2)/gChemical Oxygen Demand (COD) were obtained using a 1:10 dilution, at a C/N ratio of 60 and 70, respectively. These H-2 yields were higher than those obtained with the individual processes. The C/N ratio at the DF stage regulate not only H-2 production but also the distribution and concentrations of by-products. These metabolites, in turn, control the H-2 production during the PF. Predominant microbial population for both processes (DF: C/N = 34 Acetobacter lovaniensis, Clostridium butyricum; C/N = 39 C butyricum, Enterobacter sp, Bifidobacterium; C/N = 82 Lactobacillus casei; PF: Rhodopseudomonas palustris) were in accordance with the final metabolic products